TABLE III: Genetic modifications in mice that do not change cartilage breakdown in OA models.

Allele and/or genotype

Effect at protein level

OA feature targeted by the modification

Effect on other OA joint pathology‡

Effect on OA symptoms

OA phenotype evaluated**

Validated#
             

‡Other Joint Pathologies include: subchondral bone thickening/remodelling, osteophytes, and synovitis. The effect on cartilage erosion is not listed as it is decreased/increased/unchanged (depending on which table) in all mice/models in this Table.

**OA phenotype: post-traumatic (ptOA: ACLT = anterior cruciate ligament transection; ACLR = non-surgical mechanically induced anterior cruciate ligament rupture; DMM = surgical destabilization of the medial meniscus; iaF = intra-articular fracture; MULTI = transection of anterior and posterior cruciate ligaments, medial and lateral collateral ligaments and medial and lateral meniscectomy; s/rJL = single or repetitive joint loading without causing ligament failure; TMCL/MM = transection of the medial collateral ligament and partial or complete medial meniscectomy), over-use (ouOA: e.g. excessive or high-speed running, forced use of one limb by inhibiting load-bearing on another), spontaneous age-associated (aaOA), ovariectomy (ovxOA, high bone turnover), collagenase-induced (ciOA; more inflammatory), post-inflammatory (piOA; e.g. with sufficient time post AIA induction inflammation subsides and pathology is typical of OA), monoidoacetate-induced (miOA; chondrocyte death and marked subchondral bone erosion), papain-induced (papOA; proteolysis of cartilage aggrecan).

&It is recognized that there is continuing debate about whether some of the included models should be considered “OA”, and their inclusion here should not be considered an endorsement. However, until such time as it becomes clear which models do or do not provide information that translates to similar outcomes in human OA, these have been included.

#Validation indicates drug or therapeutic intervention e.g. comparison of antibody, inhibitor, or transgenic overexpression vs the result reported in knock out mouse. This study may have been done in mouse or another animal model of OA. ‘Yes’ means the validation study reported the expected or the same result as that in the original GM study; ‘No’ means the validation study reported a different effect.

Abbreviations: -/- = homozygous mutation, +/- = heterozygous mutation, TG = transgenic over expression.

 

References (NOTE – we need a reference style with citation noted by superscript number in the text/table BUT ALL Authors included in the reference. I can’t find one in EndNote that does this…….. any help appreciated).

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